Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Design, Synthesis, and Evaluation of Anticancer Activities of 1,2-Diborolane Derivatives for Hepatocellular Carcinoma: an in Vitro and in Silico Study(Elsevier, 2026) Sahin, Yuksel; Antika, Gizem; Aktan, Cagdas; Metin, Kubilay; Ozgener, HuseyinHepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and remains a major global health challenge due to limited treatment options and poor prognosis. Boron-containing compounds have garnered attention for their diverse biological activities, including pro-apoptotic effects in various types of cancer. In this study, we synthesized a panel of novel 1,2-N-substituted-1,2-diborolane derivatives and evaluated their antiproliferative, antimigratory, and apoptotic effects on hepatocellular carcinoma cell lines, HepG2 and Hep3B. Spectroscopic analyses confirmed the structural integrity of the synthesized compounds, revealing characteristic 1H-, 11B-, and 13C-NMR shifts consistent with boron-oxygen and boron-nitrogen bonding patterns. The derivatives, particularly compounds 2, 3, and 6, demonstrated potent and selective cytotoxicity toward HCC cells, with compound 3 exhibiting the lowest IC50 value (6.75 mu M) in HepG2 cells. Their time-dependent anti-proliferative effects were further supported by colony formation assays demonstrating long-term growth suppression, while wound healing assays revealed marked inhibition of HepG2 cell migration, indicating the compound's anti-metastatic potential. Our results demonstrate that the compound significantly induces apoptosis, modulates the expression of key apoptotic genes (Bax, Bcl-2, and caspase-3). In silico molecular docking further confirmed strong binding affinity to the anti-apoptotic Bcl-2 protein, supporting the proposed mechanism of action. These findings highlight the compound as a promising candidate for further preclinical evaluation in liver cancer therapy.Article Citation - Scopus: 27Apoptotic Effects of Resveratrol, a Grape Polyphenol, Onimatinib-Sensitive and Resistant K562 Chronic Myeloid Leukemia Cells(2012) Can,G.; Cakir,Z.; Kartal,M.; Gunduz,U.; Baran,Y.Aim: To examine the antiproliferative and apoptotic effects of resveratrol on imatinib-sensitive and imatinib-resistant K562 chronic myeloid leukemia cells. Materials and Methods: Antiproliferative effects of resveratrol were determined by the 3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5- carboxanilide inner salt (XTT) cell proliferation assay. Apoptotic effects of resveratrol on sensitive K562 and resistant K562/IMA-3 cells were determined through changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and apoptosis by annexin V-(FITC). Results: The concentrations of resveratrol that inhibited cell growth by 50% ( IC50) were calculated as 85 and 122 μM for K562 and K562/IMA-3 cells, respectively. There were 1.91-, 7.42- and 14.73-fold increases in loss of MMP in K562 cells treated with 10, 50, and 100 μM resveratrol, respectively. The same concentrations of resveratrol resulted in 2.21-, 3.30- and 7.65-fold increases in loss of MMP in K562/IMA-3 cells. Caspase-3 activity increased 1.04-, 2.77- and 4.8-fold in K562 and 1.02-, 1.41- and 3.46-fold in K562/IMA- 3 cells in response to the same concentrations of resveratrol, respectively. Apoptosis was induced in 58.7%-and 43.3% of K562 and K562/IMA-3 cells, respectively, in response to 100 μM resveratrol. Conclusion: Taken together these results may suggest potential use of resveratrol in CML, as well as in patients with primary and/or acquired resistance to imatinib.Article Citation - WoS: 4Citation - Scopus: 6Effect of Boramidic Acid Modified Carbon Nanotubes on Neurological, Morphological and Physiological Responses of Zebrafish (danio Rerio) Embryos and Larvae(Elsevier, 2024) Yigit, Aybek; Kokturk, Mine Ko; Yildirim, Serkan; Nazli, Dilek; Kiliccioglu, Metin; Sahin, Ayse; Alak, GoncaThis study aimed to determine the potential toxicological effects of carbon nanotubes (CNTs), their modifications with ethylenediamine (ED) and boric acid (BA) on aquatic organisms. Specifically, the research focused on the morphological, physiological, and histopathological-immuno-histochemical responses in zebrafish (Danio rerio) embryos and larvae, via applying different concentrations of CNTs, CNT-ED, and CNT-ED-BA (Control, 5, 10, and 20 mg/L). The results indicated that 20 mg/L CNT nanoparticles were toxic to zebrafish larvae, with mortality rates increasing with CNT and CNT-ED concentrations, reaching 36.7 % at the highest CNT concentration. The highest dose caused considerable degeneration, necrosis, DNA damage, and apoptosis, as evidenced by histopathological and immunohistochemical tests. In contrast, despite their high concentration, CNT-ED-BA nanoparticles exhibited low toxicity. Behavioral studies revealed that CNT and CNT-ED nanoparticles had a more significant impact on sensory-motor functions compared to CNT-ED-BA nanoparticles. These findings suggest that modifying the nanosurface with boric acid, resulting in boramidic acid, can reduce the toxicity induced by CNT and CNT EDArticle Citation - WoS: 6Citation - Scopus: 7A Comprehensive Study on Doxorubicin-Loaded Aspartic Acid-Coated Magnetic Fe<sub>3</Sub>o<sub>4< Nanoparticles: Synthesis, Characterization and in Vitro Anticancer Investigations(Elsevier, 2024) Jafari, Nahideh; Mohammadpourfard, Mousa; Hamishehkar, HamedMagnetic Fe3O4 nanoparticles (MNPs) hold significant potential across various scientific fields due to their notable properties. For biomedical applications, MNPs must be biocompatible, stable, and possess high magnetic potential. Aspartic acid (ASP) as a coating agent not only provides biocompatibility, stability, and high magnetic potential but also offers the potential for absorbing various drugs for targeted delivery due to its carboxyl and amino functional groups. So, in this study, we synthesized ASP-coated MNPs (ASP-MNPs) through a one-step co-precipitation method and loaded doxorubicin (DOX) onto these nanoparticles to create DOX-ASP-MNPs for targeted drug delivery. Characterization of the nanoparticle confirmed the crystal structure, spherical morphology, and improved size distribution of ASP-MNPs (8.53 +/- 2.56 nm) compared to uncoated MNPs (7.05 +/- 1.89 nm), as analyzed by XRD, FESEM, and TEM. FT-IR and zeta potential assessments (ZP = -6.3 mV for MNPs, ZP = -31.1 mV for ASP-MNPs) verified successful ASP binding, DOX loading, and nanoparticle stability. VSM analysis indicated a slight decrease in saturation magnetism after coating (51.1 emu/g) compared to MNPs (57.4 emu/g). In vitro release studies demonstrated a higher release rate (83 %) of DOX-ASP-MNPs at pH 5.2, indicating their suitability for cancerous cells. Cytotoxicity assays on A-549 cancer cell lines showed a dose-dependent response. DAPI staining revealed that free DOX caused more DNA damage. Cellular uptake studies indicated a time-dependent uptake of DOX-ASP-MNPs, higher at 3 h compared to 1 h, though lower than free DOX uptake due to different uptake pathways. Apoptosis assays over 72 h showed similar apoptotic rates for DOX-ASP-MNPs and free DOX. These findings suggest that ASP-MNPs possess enhanced physicochemical properties and effective drug delivery capabilities, making them a promising candidate for different biomedical applications, particularly targeted cancer therapy.Article Citation - WoS: 6Citation - Scopus: 6Biomolecular Fingerprints of the Effect of Zoledronic Acid on Prostate Cancer Stem Cells: Comparison of 2d and 3d Cell Culture Models(Academic Press Inc., 2024) Güler,G.; Acikgoz,E.; Mukhtarova,G.; Oktem,G.Revealing the potential of candidate drugs against different cancer types without disrupting normal cells depends on the drug mode of action. In the current study, the drug response of prostate cancer stem cells (PCSCs) to zoledronic acid (ZOL) grown in two-dimensional (2D) and three-dimensional (3D) culture systems was compared using Fourier transform-infrared (FT-IR) spectroscopy which is a vibrational spectroscopic technique, supporting by biochemical assays and imaging techniques. Based on our data, in 2D cell culture conditions, the ZOL treatment of PCSCs isolated according to both C133 and CD44 cell surface properties induced early/late apoptosis and suppressed migration ability. The CD133 gene expression and protein levels were altered, depending on culture systems. CD133 expression was significantly reduced in 2D cells upon ZOL treatment. FT-IR data revealed that the integrity, fluidity, and ordering/disordering states of the cell membrane and nucleic acid content were altered in both 2D and 3D cells after ZOL treatment. Regular protein structures decrease in 2D cells while glycogen and protein contents increase in 3D cells, indicating a more pronounced cytotoxic effect of ZOL for 2D cells. Untreated 3D PCSCs exhibited an even different spectral profile associated with IR signals of lipids, proteins, nucleic acids, and glycogen in comparison to untreated 2D cells. Our study revealed significant differences in the drug response and cellular constituents between 2D and 3D cells. Exploring molecular targets and/or drug-action mechanisms is significant in cancer treatment approaches; thus, FT-IR spectroscopy can be successfully applied as a novel drug-screening method in clinical research. © 2024 Elsevier Inc.Review Citation - WoS: 8Citation - Scopus: 8Long Noncoding Rnas in Human Cancer and Apoptosis(Bentham Science Publishers, 2023) Erdoğan, İpek; Sweef, Osama; Akgül, BünyaminGenome annotations have uncovered the production of at least one transcript from nearly all loci in the genome at some given time throughout the development. Surprisingly, many of these transcripts do not code for proteins and are relatively long in size, thus called long noncoding RNAs (lncRNAs). Next- and third-generation sequencing technologies have amassed numerous lncRNAs expressed under different phenotypic conditions, yet many remain to be functionally characterized. LncRNAs regulate gene expression by functioning as scaffold, decoy, signaling, and guide molecules both at the transcriptional and post-transcriptional levels, interacting with different types of macromolecules, such as proteins, DNA, and RNA. Here, we review the potential regulatory role of lncRNAs in apoptosis and cancer as some of these lncRNAs may have the diagnostic and therapeutic potential in cancer.Book Part Citation - Scopus: 5Epitranscriptomics Changes the Play: M6a Rna Modifications in Apoptosis(Springer, 2022) Akçaöz, Azime; Akgül, BünyaminApoptosis is a form of programmed cell death that is essential for cellular and organismal homeostasis. Any irregularities that disturb the balance between apoptosis and cell survival have severe implications, such as improper development or life-threatening diseases. Thus, it is highly critical to maintain a proper rate of apoptosis throughout development. In fact, several complex transcriptional and posttranscriptional mechanisms exist in eukaryotes to critically regulate the rate of apoptotic processes. Recent studies suggest that not only RNA sequences but also their modifications, such as m6A methylation, play a fundamental role in these transcriptional and posttranscriptional processes. A specific set of proteins, called writer, eraser, and reader of m6A marks, modulate the rate of apoptosis by determining the m6A repertoire and the fate of certain transcripts associated with apoptosis. In this Review, we will cover the dynamic m6A RNA modifications and their impact on modulation of apoptosis.
